New Angelman syndrome therapy proposed

Isis Pharma approach helps mouse models of genetic disease

A potential therapy for Angelman syndrome, a baffling genetic disease that impairs intellectual development, has been proposed by scientists including researchers at Isis Pharmaceuticals.

The treatment, tested in mice, activates a gene that restores some of the neurological activity reduced in Angelman syndrome, which affects an estimated 1 in 12,000 to 1 in 20,000 people.

A paper describing the research was published Dec. 1 in the journal Nature. The first authors are Linyan Meng of Baylor College of Medicine and Amanda J. Ward of Isis. Senior authors are Arthur L. Beaudet of Baylor and Frank Rigo of Isis. Seung Chun and C. Frank Bennett of Isis also authored the paper.

In the Nature study, the Isis and Baylor scientists describe a method to compensate, by activating the paternal UBE3A gene. The antisense approach is to inactivate a long non-coding RNA called UBE3A-ATS that normally silences the paternal gene. This facilitates gene expression, allowing production of a protein the gene codes for.

The researchers developed an antisense molecule designed to bind to and inactivate UBE3A-ATS. The molecule was injected into the central nervous system of Angelman syndrome mice. Production of the UBE3A protein was boosted, although it didn’t reach normal levels. A single dose increased production for 16 weeks.